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Gastric cancer in the era of molecularly targeted agents: current drug development strategies

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Abstract

Gastric cancer is the second most common cause of cancer death worldwide with approximately one million cases diagnosed annually. Despite considerable improvements in surgical techniques, innovations in clinical diagnostics and the development of new chemotherapy regimens, the clinical outcome for patients with advanced gastric cancer and cancer of the GEJ is generally poor with 5-year survival rates ranging between 5 and 15%. The understanding of cancer relevant events has resulted in new therapeutic strategies, particularly in developing of new molecular targeted agents. These agents have the ability to target a variety of cancer relevant receptors and downstream pathways including the epidermal growth factor receptor (EGFR), the vascular endothelial growth factor receptor (VEGFR), the insulin-like growth factor receptor (IGFR), the c-Met pathway, cell-cycle pathways, and down-stream signalling pathways such as the Akt-PI3k-mTOR pathway. In the era of new molecularly targeted agents this review focuses on recent developments of targeting relevant pathways involved in gastric cancer and cancer of the GEJ.

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References

  • Amemiya H, Kono K, Itakura J et al (2002) C-Met expression in gastric cancer with liver metastasis. Oncology 63(3):286–296. doi:10.1159/000065477

    Article  PubMed  CAS  Google Scholar 

  • Attard G, Fong PC, Molife R et al (2006) Phase I trial involving the pharmacodynamic (PD) study of circulating tumour cells, of CP-751, 871 (C), a monoclonal antibody against the insulin-like growth factor 1 receptor (IGF-1R), with docetaxel (D) in patients (p) with advanced cancer. J Clin Oncol 24:3023

    Google Scholar 

  • Bae SH, Ryoo HM, Kim MK et al (2008) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in gastric cancer cell lines. Oncol Rep 19(4):1027–1032

    PubMed  CAS  Google Scholar 

  • Bang Y, Kang Y, Kang W et al (2007) Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study. J Clin Oncol 25:4603. doi:10.1200/JCO.2007.10.8688

    Article  Google Scholar 

  • Bang Y, Chung H, Sawaki A et al (2008) HER2-positivity rates in advanced gastric cancer (GC): results from a large international phase III trial. J Clin Oncol 26:4526

    Google Scholar 

  • Bolden JE, Peart MJ, Johnston RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5(9):769–784. doi:10.1038/nrd2133

    Article  PubMed  CAS  Google Scholar 

  • Bramhall SR, Hallissey MT, Whiting J et al (2002) Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br J Cancer 86(12):1864–1870. doi:10.1038/sj.bjc.6600310

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660. doi:10.1038/nm0603-653

    Article  PubMed  CAS  Google Scholar 

  • Carpenter G, Cohen S (1990) Epidermal growth factor. J Biol Chem 265:7709–7712

    PubMed  CAS  Google Scholar 

  • Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42(3):113–185. doi:10.1080/10409230701340019

    Article  PubMed  CAS  Google Scholar 

  • Cejka D, Preusser M, Woehrer A et al. (2008) Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther 7(9) (epub ahead of print)

  • Cheema HS, Motwani MV et al. (2004) Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase (HDAC) inhibitor, induces a unique mitotic effect and potentiates flavopiridol (F) induced apoptosis. Proc Am Assoc Cancer Res 45: 2443

    Google Scholar 

  • Cohenuram MK, Lacy J (2008) FOLFOX6 and bevacizumab (FOLFOX6/B) for metastatic esophageal (E), gastroesophageal (GE), and gastric (G) adenocarcinoma: a single institution’s initial clinical experience. Proc GI ASCO: 74

  • Cortés-Funes H, Rivera F, Alés I et al (2007) Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/neu overexpression/amplification. J Clin Oncol 25:4613

    Google Scholar 

  • Dar AA, Zaika A, Piazuela MB et al (2008) Frequent overexpression of aurora kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer 112(8):1688–1698. doi:10.1002/cncr.23371

    Article  PubMed  CAS  Google Scholar 

  • de Mingo M, Morán A, Sánchez-Pernaute A et al (2007) Expression of MMP-9 and TIMP-1 as prognostic markers in gastric carcinoma. Hepatogastroenterology 54(73):315–319

    PubMed  Google Scholar 

  • Dragovich T, McCoy S, Fenoglio-Preiser CM et al (2006) Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol 24(30):4922–4927. doi:10.1200/JCO.2006.07.1316

    Article  PubMed  CAS  Google Scholar 

  • Eskens FA, Mom CH, Planting AS et al (2008) A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 98(1):80–85. doi:10.1038/sj.bjc.6604108

    Article  PubMed  CAS  Google Scholar 

  • Fujita T, Doihara H, Washio K et al (2007) Antitumor effects and drug interactions of the proteasome inhibitor bortezomib (PS341) in gastric cancer cells. Anticancer Drugs 18(6):677–686. doi:10.1097/CAD.0b013e32808bf9d8

    Article  PubMed  CAS  Google Scholar 

  • Gong SJ, Jin CJ, Rha SY et al (2004) Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines. Cancer Lett 214(2):215–224. doi:10.1016/j.canlet.2004.04.029

    Article  PubMed  CAS  Google Scholar 

  • Grimber A, Cohen P (2000) Role of insulin-like growth factor and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183:1–9. doi:10.1002/(SICI)1097-4652(200004)183:1<1::AID-JCP1>3.0.CO;2-J

    Article  Google Scholar 

  • Haluska P, Shaw H, Batzel GN et al (2007) Phase I dose escalation study of the anti-IGF-1R monoclonal antibody CP-751, 871 in patients with refractory solid tumors. J Clin Oncol 25:3586

    Google Scholar 

  • Hammad N, Philip PA, Shields AF et al. (2008) A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and gastroesophageal junction (GEJ) cancer. Proc GI ASCO: 30

  • Han Z, Wu K, Shen H et al (2008) Akt1/protein kinase B alpha is involved in gastric cancer progression and cell proliferation. Dig Dis Sci 53(7):1801–1810. doi:10.1007/s10620-007-9824-2

    Article  PubMed  CAS  Google Scholar 

  • Han SW, Oh DY, Im SA et al (2009) Phase II study and biomarker analysis of cetuximab in combination with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 100(2):298–304. doi:10.1038/sj.bjc.6604861

    Article  PubMed  CAS  Google Scholar 

  • Hattori Y, Itoh H, Uchino S et al (1996) Immunohistochemical detection of K-sam protein in stomach cancer. Clin Cancer Res 2(8):1373–1381

    PubMed  CAS  Google Scholar 

  • Hecht JR, Urba SG, Koehler M et al. (2008) Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: phase II efficacy and biomarker analyses. Proc GI ASCO: 43

  • Hecht JR, Mitchell E, Chidiac T et al (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27(5):672–680. doi:10.1200/JCO.2008.19.8135

    Article  PubMed  CAS  Google Scholar 

  • Hinoda Y, Sasaki S, Ishida T et al (2004) Monoclonal antibodies as effective therapeutic agents for solid tumors. Cancer Sci 96:443–446

    Google Scholar 

  • Hirata A, Ogawa S, Kometani T et al (2002) ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 62(9):2554–2560

    PubMed  CAS  Google Scholar 

  • Inoue T, Kataoka H, Goto K et al (2004) Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue. Cancer Sci 95(10):803–808. doi:10.1111/j.1349-7006.2004.tb02185.x

    Article  PubMed  CAS  Google Scholar 

  • Iqbal S, Goldman B, Lenz HJ et al (2007) S0413: a phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol 25:4621

    Google Scholar 

  • Iwamoto J, Mizokami Y, Takahashi K et al (2008) The effects of cyclooxygenase2-prostaglandinE2 pathway on Helicobacter pylori-induced urokinase-type plasminogen activator system in the gastric cancer cells. Helicobacter 13(3):174–182. doi:10.1111/j.1523-5378.2008.00597.x

    Article  PubMed  CAS  Google Scholar 

  • Jang YJ, Kim YS, Kim WH et al (2006) Oncogenic effect of Polo-like kinase 1 expression in human gastric carcinomas. Int J Cancer 29(3):589–594

    CAS  Google Scholar 

  • Jhawer MP, Ilson D, Robinson E et al. (2008) Interim results of a phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF), and bevacizumab (BEV) in patients with metastatic gastroesophageal (GE) adenocarcinoma. Proc GI ASCO: 109

  • Jhawer MP, Kindler HL, Wainberg ZA et al (2008b) Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): interim results of a multicenter phase II study. J Clin Oncol 26:4572. doi:10.1200/JCO.2007.15.5655

    Article  Google Scholar 

  • Jones HE, Gee JMW, Hutcheson IR et al (2006) Growth factor receptor interplay and resistance in cancer. Endocr Relat Cancer 13(Suppl 1):S45–S51. doi:10.1677/erc.1.01275

    Article  PubMed  CAS  Google Scholar 

  • Kamada K, Yamada Y, Hirao T et al (2004) Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep 12(3):593–599

    PubMed  CAS  Google Scholar 

  • Karayiannakis AJ, Syrigos KN, Polychronidis A et al (2002) Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery. Ann Surg 236(1):37–42. doi:10.1097/00000658-200207000-00007

    Article  PubMed  Google Scholar 

  • Kim JW, Kim HP, Im SA et al. (2008) The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett (e-pub ahead of print)

  • Kuwano T, Nakao S, Yamamoto H (2004) Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J 18(2):300–310. doi:10.1096/fj.03-0473com

    Article  PubMed  CAS  Google Scholar 

  • Lang SA, Klein D, Moser C et al (2007a) Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Mol Cancer Ther 6(3):1123–1132. doi:10.1158/1535-7163.MCT-06-0628

    Article  PubMed  CAS  Google Scholar 

  • Lang SA, Gaumann A, Koehl GE et al (2007b) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. doi:10.1002/ijc.22442

    Article  PubMed  CAS  Google Scholar 

  • Lax AJ, Thomas W (2002) How bacteria could cause cancer: one step at a time. Trends Microbiol 10(6):293–299. doi:10.1016/S0966-842X(02)02360-0

    Article  PubMed  CAS  Google Scholar 

  • Lordick F, Lorenzen S, Hegewisch-Becker S et al (2007) Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group. J Clin Oncol 26:4526

    Google Scholar 

  • Macarulla T, Ramos FJ, Tabernero J (2008) Aurora kinase family: a new target for anticancer drug. Recent Patents Anticancer Drug Discov 3(2):114–122

    Article  CAS  Google Scholar 

  • Mani A, Gelmann EP (2005) The Ubiquitin-Proteasome pathway and its role in cancer. J Clin Oncol 23(21):4776–4789. doi:10.1200/JCO.2005.05.081

    Article  PubMed  CAS  Google Scholar 

  • Mann JR, Backlund MG, DuBois RN (2005) Mechanisms of disease: inflammatory mediators and cancer prevention. Nat Clin Pract Oncol 2(4):202–210. doi:10.1038/ncponc0140

    Article  PubMed  CAS  Google Scholar 

  • Marks PA, Jiang X (2005) Histone deacetylase inhibitors in programmed cell death and cancer therapy. Cell Cycle 4(4):549–551

    PubMed  CAS  Google Scholar 

  • Marumoto T, Hirota T, Morisaki T et al (2002) Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes Cells 7:1173–1182. doi:10.1046/j.1365-2443.2002.00592.x

    Article  PubMed  CAS  Google Scholar 

  • Matsubara J, Yamada Y, Hirashima Y et al (2008) Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer. Clin Cancer Res 14(10):3022–3029. doi:10.1158/1078-0432.CCR-07-1898

    Article  PubMed  CAS  Google Scholar 

  • Maulik G, Shrikhande A, Kijima T et al (2002) Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev 13(1):41–59. doi:10.1016/S1359-6101(01)00029-6

    Article  PubMed  CAS  Google Scholar 

  • McCarty MF, Wey J, Stoeltzing O et al (2004) ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor tyrosine kinase, inhibits orthotopic growth and angiogenesis of gastric cancer. Mol Cancer Ther 3(9):1041–1048

    PubMed  CAS  Google Scholar 

  • Miremadi A, Oestergaard MZ, Pharoah PD et al (2007) Cancer genetics of epigenetic genes. Hum Mol Genet 16(1):R28–R49. doi:10.1093/hmg/ddm021

    Article  PubMed  CAS  Google Scholar 

  • Moehler M, Hartmann JT, Lordick F et al. (2009) Sunitinib in patients with chemorefractory metastatic gastric cancer: preliminary results of an open-label, prospective non-randomised multicentre AIO Phase II trial. Proc GI ASCO: 61

  • Morgensztern D, McLeod HL (2005) PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 16(8):797–803. doi:10.1097/01.cad.0000173476.67239.3b

    Article  PubMed  CAS  Google Scholar 

  • Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356(2):115–124. doi:10.1056/NEJMoa065044

    Article  PubMed  CAS  Google Scholar 

  • Muro K, Boku N, Yamada Y et al (2008) Multicenter phase II study of RAD001 for previously treated metastatic gastric cancer (MGC): preliminary results. J Clin Oncol 26:4541

    Google Scholar 

  • Nakajima M, Sawada H, Yamada Y et al (2000) The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 85:1894–1902

    Google Scholar 

  • Nakamura K, Yashiro M, Matsuoka T et al (2006) A novel molecular targeting compound as K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, for Scirrhous gastric cancer. Gastroenterology 131(5):1530–1541. doi:10.1053/j.gastro.2006.08.030

    Article  PubMed  CAS  Google Scholar 

  • Ocean AJ, Schnoll-Sussman F, Chen X et al. (2007) Phase II study of PS-341 (VELCADE, bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA). Proc GI ASCO: 45

  • Oki E, Baba H, Tokunaga E et al (2005) Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. Int J Cancer 117(3):376–380. doi:10.1002/ijc.21170

    Article  PubMed  CAS  Google Scholar 

  • Park JH, Jung Y, Kim TY et al (2004) Class I histone deacetylase-selective novel synthetic inhibitors potently inhibit human tumor proliferation. Clin Cancer Res 10(15):5271–5281. doi:10.1158/1078-0432.CCR-03-0709

    Article  PubMed  CAS  Google Scholar 

  • Pinto C, Di Fabio F, Siena S et al (2007) Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 18(3):510–517. doi:10.1093/annonc/mdl459

    Article  PubMed  CAS  Google Scholar 

  • Pinto C, Di Fabio F, Barone C et al. (2008) Phase II study of cetuximab in combination with cisplatin/docetaxel as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (DOCETUX Study): preliminary results. Proc GI ASCO: 34

  • Presta LG, Chen H, O’Connor SJ et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599

    PubMed  CAS  Google Scholar 

  • Rao S, Starling N, Cunningham D et al. (2008) Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. Br J Cancer (epub ahead of print)

  • Rojo F, Tabernero J, Albanell J et al (2006) Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J Clin Oncol 24(26):4309–4316. doi:10.1200/JCO.2005.04.2424

    Article  PubMed  CAS  Google Scholar 

  • Saltz LB, Meropol NJ, Loehrer PJ et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208. doi:10.1200/JCO.2004.10.182

    Article  PubMed  CAS  Google Scholar 

  • Saltz LB, Lenz HJ, Kindler HL et al (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 Study. J Clin Oncol 25:4557–4561. doi:10.1200/JCO.2007.12.0949

    Article  PubMed  CAS  Google Scholar 

  • Schwartz GK, Ilson D, Saltz L et al (2001) Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 19(7):1985–1992

    PubMed  CAS  Google Scholar 

  • Senderowicz AM (2000) Small molecule modulators of cyclin-dependent kinases for cancer therapy. Oncogene 19(56):6600–6606. doi:10.1038/sj.onc.1204085

    Article  PubMed  CAS  Google Scholar 

  • Shah MA, Ramanathan RK, Ilson DH et al (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(33):5201–5206. doi:10.1200/JCO.2006.08.0887

    Article  PubMed  CAS  Google Scholar 

  • Song J, Noh JH, Lee JH et al (2005) Increased expression of histone deacetylase 2 is found in human gastric cancer. APMIS 113(4):264–268. doi:10.1111/j.1600-0463.2005.apm_04.x

    Article  PubMed  CAS  Google Scholar 

  • Stein A, Al-Batran SE, Arnold D et al. (2007) Cetuximab with irinotecan as salvage therapy in heavily pretreated patients with metastatic gastric cancer. Proc GI ASCO: 47

  • Sun W, Powell ME, O’Dwyer P et al (2008) A phase II study: combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203). J Clin Oncol 26:4535

    Article  Google Scholar 

  • Tahara E (2004) Genetic pathways of two types of gastric cancer. IARC Sci Publ 157:327–349

    PubMed  Google Scholar 

  • Takai N, Hamanaka R, Yoshimatsu J et al (2005) Polo-like kinases (Plks) and cancer. Oncogene 24(2):287–291. doi:10.1038/sj.onc.1208272

    Article  PubMed  CAS  Google Scholar 

  • Tanner M, Hollmen M, Junttila TT et al (2005) Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16:273–278. doi:10.1093/annonc/mdi064

    Article  PubMed  CAS  Google Scholar 

  • Tebbutt NC, Sourjina T, Strickland AH et al (2008) ATTAX2: docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophago-gastric cancer—final results of a multicentre phase II trial by the AGITG. J Clin Oncol 26:15554

    Google Scholar 

  • Thomas JP, Tutsch KD, Cleary JF et al (2002) Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol. Cancer Chemother Pharmacol 50(6):465–472. doi:10.1007/s00280-002-0527-2

    Article  PubMed  CAS  Google Scholar 

  • Tierney GM, Griffin NR, Stuart RC et al (1999) A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer. Eur J Cancer 35(4):563–568. doi:10.1016/S0959-8049(99)00007-6

    Article  PubMed  CAS  Google Scholar 

  • Tol J, Koopman M, Cats A et al. (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563–572

    Google Scholar 

  • Tortora G, Ciardiello F, Gasparini G (2008) Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat Clin Pract Oncol 5(9):521–530. doi:10.1038/ncponc1161

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi S, Neckers L (2007) Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci 98(10):1536–1539. doi:10.1111/j.1349-7006.2007.00561.x

    Article  PubMed  CAS  Google Scholar 

  • Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664. doi:10.1200/JCO.2006.08.1620

    Article  PubMed  Google Scholar 

  • Wada N, Otani Y, Kubota T et al (2003) Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition. Clin Exp Metastasis 20(5):431–435. doi:10.1023/A:1025453500148

    Article  PubMed  CAS  Google Scholar 

  • Wang HK (2001) Flavopiridol. National Cancer Institute. Curr Opin Invest Drugs 2(8):1149–1155

    CAS  Google Scholar 

  • Wang WH, Huang JQ, Zheng GF et al (2003) Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 95(23):1784–1791

    PubMed  CAS  Google Scholar 

  • Weichert W, Ullrich A, Schmidt M et al (2006) Expression patterns of polo-like kinase 1 in human gastric cancer. Cancer Sci 97(4):271–276. doi:10.1111/j.1349-7006.2006.00170.x

    Article  PubMed  CAS  Google Scholar 

  • Weichert W, Röske A, Gekeler V et al (2008) Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol 9(2):139–148. doi:10.1016/S1470-2045(08)70004-4

    Article  PubMed  CAS  Google Scholar 

  • Woell E, Greil R, Eisterer W et al (2008) Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer: first results of a multicenter phase II trial (AGMT Gastric-2). J Clin Oncol 26:15587

    Google Scholar 

  • Yap TA, Harris D, Barriuso J et al (2008) Phase I trial to determine the dose range for the c-Met inhibitor ARQ 197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule. J Clin Oncol 26:3584

    Google Scholar 

  • Zou XM, Li YL, Wang H et al (2008) Gastric cancer cell lines induced by trichostatin A. World J Gastroenterol 14(30):4810–4815. doi:10.3748/wjg.14.4810

    Article  PubMed  CAS  Google Scholar 

  • Zucker S, Cao J, Chen WT (2000) Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19(56):6642–6650. doi:10.1038/sj.onc.1204097

    Article  PubMed  CAS  Google Scholar 

  • Zuo DS, Dai J, Bo AH et al (2003) Significance of expression of heat shock protein90alpha in human gastric cancer. World J Gastroenterol 9(11):2616–2618

    PubMed  CAS  Google Scholar 

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Dr Hendrik-Tobias Arkenau has no conflict of interest.

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Arkenau, HT. Gastric cancer in the era of molecularly targeted agents: current drug development strategies. J Cancer Res Clin Oncol 135, 855–866 (2009). https://doi.org/10.1007/s00432-009-0583-7

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